(1) Field of the Invention
The antibiotic compound of this invention is a derivative of p-hydroxy-hetacillin and amoxicillin.
(2) Description of the Prior Art
Hetacillin is a penicillin derivative known, in the acid form, as D-6-(2,2-dimethyl-5-oxo-4-phenyl-1-imidazolidinyl)penicillanic acid. This compound, i.e., hetacillin, and many closely related compounds and the preparation thereof are disclosed in U.S. Pat. No. 3,198,804. Esters of benzylpenicillins are disclosed in British Pat. No. 1,003,479 and U.S. Pat. No. 2,650,218, and acyloxymethyl esters of ampicillin are discussed by W. v. Daehne et al. in J. Med. Chem., 13, (4), 607-612 (1970). This publication also refers to early publications on the hydrolysis of esters. The pivaloyloxymethyl ester of ampicillin is also disclosed in U.S. Pat. Nos. 3,660,575 and 3,697,507. Various penicillin esters are also disclosed, for example, in U.S. Pat. No. 3,528,965 and U.K. No. 1,267,936. Various esters of 6-aminopenicillanic acid have been disclosed, for example, in U.S. Pat. Nos. 3,652,546 and 3,399,207. The crystalline toluene-p-sulphonate of the methoxymethyl ester of 6-aminopenicillanic acid was described by Jackson et al., Chemical Communications, 1970, pages 14-15. Methoxymethyl benzylpenicillinate and other penicillin esters are described by Jansen et al., J. Chem. Soc., 2127-32 (1965) and that publication refers to earlier publications such as Johnson, J. Amer. Chem. Soc., 75, 3636 (1953) and Barnden et al., J. Chem. Soc., 3733 (1953). The Jansen et al. publication is referred to in U.K. No. 1,217,143 published Dec. 31, 1970 (but not in the corresponding U.S. Pat. No. 2,650,218) in its generic disclosure on page 2 which names various specific esters of penicillins, including methoxymethyl, and suggests acylation of those and other esters of 6-aminopenicillanic acid (6-APA) with "any of the acyl groups found in the side chains of known antibacterial penicillins, especially the group of" the formula for D-(-)-2-phenylglycine which occurs in ampicillin.
Amoxicillin [also known as D-6-(p-hydroxy-.alpha.-aminophenylacetamido)penicillanic acid] is disclosed in U.S. Pat. Nos. 3,192,198 and 3,674,776; p-hydroxyhetacillin is disclosed in U.K. No. 1,224,619.
Subsequent to the filing on Sept. 13, 1971 of the parent of this application in the United States there appeared abroad applications corresponding to said parent application U.S. Ser. No. 180,070 as exemplified by U.S. Pat. No. 3,996,236 and by Belgium No. 788,720 to Bristol-Myers Company reported and abstracted as Farmdoc 18226U by Derwent Publications Ltd, Rochdale House, 128 Theobalds Road, London WC1X 8RP, England, in the issue of Central Patents Index--Basic Abstracts Journal--B--Farmdoc dated May 17, 1973. In the issue of Feb. 8, 1973 Belgium No. 784,800 to Yamanouchi Pharmaceutical Co., Ltd. was abstracted as Farmdoc 81300T; this Belgian patent generically claims, inter alia, compounds of the formula ##STR1## wherein Y is, inter alia, lower alkyl and also contains working examples wherein Y is ethyl and some higher homologs and contains on page 4 a reference to the use of chloromethyl methyl ether (Y equals methyl).